Responsive to this RFA, we propose to focus on the discovery of cognitive, behavioral, and neurobiological mechanisms underlying adolescent literacy that can facilitate identification, prevention and remediation of adolescent reading difficulties. Our approach is to extend our previous work and our group's acknowledged strengths in classification, neurobiological, and longitudinal studies of literacy to address the two overarching questions of this RFA: 1. What characterizes adolescent struggling readers? and 2. How do factors affecting literacy change over time? Our research strategy uses a prospective longitudinal study design of a large population, well characterized as young school-age children and whom we propose to assess as adolescents; achievement and processing variables characterizing empirically-derived subtypes of reading disability (RD); state-of-the-art functional and structural brain imaging methodologies integrated with assessment of neural response to an intervention; and measures of outcome in multiple domains. We envision this project serving as a pivotal resource to other members of the adolescent literacy network who are more emphasizing intervention studies. In-depth knowledge of the subtypes, their stability over time, neurobiological response to intervention, and determinants of outcome should play a critical role in better understanding, interpreting, and more precisely targeting interventions for specific subgroups of adolescent struggling readers and developing prevention approaches for subgroups of younger struggling readers. Utilization and application of the characterization variables used in this study will allow investigators in the network to probe group- and type-by-treatment interactions and to more precisely determine the efficacy of, and match specific treatments to, specific groups of struggling adolescent readers. The sample, measures and longitudinal framework allow us to address three inter-related specific aims: 1) To identify and determine the temporal stability of subgroups and subtypes of adolescent RD; 2) To characterize brain-behavior relationships in groups and types of adolescent struggling readers, brain mechanisms underlying skill, compensation and persistence, and response to intervention in adolescents with RD; and 3) To determine the nature and determinants of outcome in adolescence of childhood RD and the later outcome of adolescent RD. [unreadable] [unreadable] [unreadable]